Recent observations indicate that mouse macrophage procoagulant activity is directly correlated with the expression of a cell associated plasminogen activator (PA) and inversely correlated with soluble PA activity. Stimulated macrophages thus concurrently influence fibrin deposition and the pattern of its resorption. although macrophages and fibrin are prominently involved in several physiological and pathological situations in man, human tissue macrophage have not been examined for their capability to express procoagulant and plasminogen activator activities. We propose to define the pathways by which human alveolar macrophages modulate fibrin turnover with emphasis on the immunological characterization of a plasminogen activator inhibitor recently discovered by the investigator in murine macrophages. We will determine whether macrophages, both freshly isolated and after stimulation in vitro, concurrently or differentially express procoagulant, cell surface associated and soluble PA activities. We will also determine in normal or stimulated alveolar macrophages contain intracellular PA inhibitor and if macrophages can be induced to synthesize and secrete this inhibitor in vitro. If PA inhibitor is observed in human macrophages, we will by immunoprecipitation techniques compare it to the known proteinase inhibitors of blood and determine if it is a normal component of human blood. In addition, as fibrin turnover appears to be important in tissue repair and fibrotic processes, we will examine the expression of fibroblast growth promoting factors and fibronectin by macrophages and determine if the expression of these factors correlates with their modulation of fibrin turnover. The propositions which underlie this proposal are first that the interaction of macrophages with fibrin is an important part of the contribution of macrophages to host defense and tissue repair and that this interaction needs better definition in humans. Second, that the utilization of a human source of plasminogen activator inhibitor for study is important to its further characterization. And lastly, that the acquisition of a profile of the activities of macrophage derived factors that influence fibrin turnover and tissue repair is necessary to understand how the pluripotential nature of macrophages is coordinated in vivo towards an effective purpose.